细胞因子风暴及其治疗方法的研究进展

Research advances of cytokine storm and therapeutics

由致病因素激活人体先天性和适应性免疫反应所导致的炎症反应是人体的第一道防线。然而,某些病原体(如SARS-CoV-2、SARS-CoV、MERS-CoV和登革热病毒等)会在宿主内引发威胁生命的"细胞因子风暴",进而引起多器官功能衰竭并最终导致死亡。一些内源性消炎调控因子,如消退素、脂氧素、环氧不饱和脂肪酸等,可以调节组织损伤而不破坏有益的炎症应答,为炎性疾病的治疗提供了新途径。其中可溶性环氧化物水解酶(soluble epoxide hydrolase,sEH)抑制剂可以稳定环氧二十碳三烯酸(epoxyeicosatrienoic acids,EETs),通过多种机制调控细胞因子,重塑机体致炎/抗炎平衡,从而发挥消退炎症的作用,有望成为治疗细胞因子风暴的新靶点。本文综述了细胞因子风暴的病理机制以及目前潜在的治疗方法,希望为相关疾病的诊断和治疗提供新的思路。

Inflammation is the body′s first line of defense against infection or injury by activating the innate and adaptive immune responses.Some pathogens(SARS-CoV-2,SARS-CoV,MERS-CoV and dengue viruses,etc.) can trigger life-threatening "cytokine storm",which leads to serious pathological conditions and ultimately death.Therefore,controlling the inflammatory immune response is expected to play a positive role in managing the relevant disease.Some candidate drugs have shown promise in managing cytokine storm in the clinic.In addition,some endogenous specialized pro-resolving mediators(such as resolvins,lipoxin,and epoxy unsaturated fatty acids) can regulate tissue damage without disrupting the beneficial inflammatory response,providing a novel approach for the treatment of cytokine storm.Among them,soluble epoxide hydrolase inhibitors can stabilize epoxyeicosatrienoic acids,stimulate the production of pro-resolving mediators,block the inflammatory cascade and restore the balance of inflammation/anti-inflammatory via multiple mechanisms,and thus have great potential for the treatment of cytokine storms.This review summarized the pathogenesis of cytokine storm and the potential therapeutics which may prove useful in the future.